S. Calvo Blanco¹, O. Nobus1, L. Verlinden2, I. Stockmans2, K. Moermans2, F. Stappers3, L. Crombez4, C. Vercruysse5, E. Gracey3, D. Elewaut3, A. De Spiegeleer4, R. I. Dmitriev6, G. T’Sjoen7, L. Devisscher8, S. Stegen2, V. Dubois¹
¹Basic and Translational Endocrinology (BaTE) Laboratory, Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Belgium
2Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Faculty of Medicine, KU Leuven, Belgium
3VIB Center for Inflammation Research and Unit for Molecular Immunology and Inflammation, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Belgium
4Translational Research in Immunosenescence, Gerontology and Geriatrics (TRIGG) Group, Geriatric Department, Ghent University Hospital, Belgium
5Clinical Tissue and Cell Culture Core, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences , Ghent University, Belgium
6Tissue Engineering and Biomaterials Lab, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences , Ghent University, Belgium
7Department of Endocrinology and Center for Sexology and Gender, Ghent University Hospital, Belgium
8Gut-Liver ImmunoPharmacology (GLIPh) Unit, Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Belgium
The trans gender population experiences a gender identity that differs from their designated sex at birth. Gender-affirming therapy in trans gender adolescents may include puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) followed by gender-affirming hormones (GAH). In trans individuals assigned male at birth, the combined usage of a progestogen, e.g. the natural progesterone (P4) or the synthetic medroxyprogesterone acetate (MPA), alongside the standard estrogen therapy has become popular due to a presumed enhancedfeminization. However, the impact of this progestogen addition on the musculoskeletal system and metabolic tissues is unclear. Therefore, we will investigate the effects of estrogen combined with a progestogen on different organ systems using a mouse model mimicking the clinical trajectory of trans girls.
Prepubertal 4-week-old male mice will be treated with the GnRHa degarelix (DGX) to suppress puberty, followed by the administration of estradiol (E2) combined with a progestogen (P4 or MPA) from 8 weeks of age. Their phenotype at 16 weeks of age will be compared to puberty-suppressed male mice treated with E2 alone, and to vehicle-treated male and female animals(controls for native sex and gender, respectively). The weight of sex hormone-sensitive tissues will be recorded to confirm treatment effectiveness. To investigate systemic metabolic changes, body composition will be determined by MRI and a glucose tolerance test will be performed. The impact of the hormonal manipulations on muscle strength and fatigue will be assessed by grip strength and treadmill endurance tests. Effects on the skeleton will be investigated through microcomputed tomography, three-point bending and (dynamic) histomorphometry.
In conclusion, this study will shed light on the effects of progestogen addition to the standard estrogen therapy in adolescent gender transition. These novel insights may ultimately beleveraged for optimizing medical care of trans youth.